Results of our previous studies with DES-treated neonatal mice have revealed an enhanced nuclear retention of estrogen receptor in estrogen target tissues. This and other information suggest a general hypothesis for estrogen-induced carcinogenesis. It is proposed that DES and other estrogens cause permanent changes in estrogen target cells when administered during critical stages of development, and that estrogen-induced alteration of nuclear estrogen receptor retention may be a significant factor contributing to tumorigenesis during estrogen exposure in adult life. Experiments have been designed to: 1) Obtain new information on the regulation of estrogen receptor and progesterone receptor ontogeny during postnatal development in the hamster; 2) Identify the permanent alterations in estrogen-receptor and progesterone-receptor systems which result after exposure to DES and other estrogens during critical times of development; 3) Test the hypothesis that DES-induced developmental changes increase the risk of tumor formation during exposure to estrogen later in life; 4) Develop new methods for preventing tumorigenesis based on progresterone and antiestrogen therapy.